Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in e Presence of Endogenous Electric Fields in Mouse Brains
Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in e Presence of Endogenous Electric Fields in Mouse Brains
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DOI：
10.1523/eneuro.0382-19.2019
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发表时间：
2019-11-01
期刊：
影响因子：
3.4
通讯作者：
Morshead, Cindi M.
中科院分区：
文献类型：
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作者：
Iwasa, Stephanie N.;Rashidi, Abdolazim;Morshead, Cindi M.
电场（EFs）可以引导细胞迁移，在发育和组织修复过程中至关重要。我们以前报道过神经前体细胞（NPC）是电敏感细胞，可以在体外使用电荷平衡的电刺激进行快速和定向迁移到阴极。在这里，我们调查的能力，电刺激直接神经前体迁移在小鼠大脑中的体内。为了可视化迁移，将荧光成年鼠神经前体移植到成年雄性小鼠的胼胝体上，并将皮质内铂丝电极植入注射部位的内侧（阴极）和外侧（阳极）。我们应用电荷平衡双相单极刺激波形，每天3次，持续3或6 d。无论刺激，移植的神经前体细胞有倾向迁移横向沿着胼胝体，并施加刺激影响迁移。进一步的研究发现，内源性EF沿着胼胝体与横向迁移，这表明，应用EF将需要克服内源性线索。与刺激和植入的非刺激脑相比，植入的细胞分化和增殖或电极导线和注射部位附近的炎性细胞数量没有差异。我们的研究结果支持内源性和应用的EFs是设计体内组织修复细胞疗法的重要考虑因素。
Electric fields (EFs) can direct cell migration and are crucial during development and tissue repair. We previously reported neural precursor cells (NPCs) are electrosensitive cells that can undergo rapid and directed migration towards the cathode using charge-balanced electrical stimulation in vitro. Here, we investigate the ability of electrical stimulation to direct neural precursor migration in mouse brains in vivo. To visualize migration, fluorescent adult murine neural precursors were transplanted onto the corpus callosum of adult male mice and intracortical platinum wire electrodes were implanted medial (cathode) and lateral (anode) to the injection site. We applied a charge-balanced biphasic monopolar stimulation waveform for three sessions per day, for 3 or 6 d. Irrespective of stimulation, the transplanted neural precursors had a propensity to migrate laterally along the corpus callosum, and applied stimulation affected that migration. Further investigation revealed an endogenous EF along the corpus callosum that correlated with the lateral migration, suggesting that the applied EF would need to overcome endogenous cues. There was no difference in transplanted cell differentiation and proliferation, or inflammatory cell numbers near the electrode leads and injection site comparing stimulated and implanted non-stimulated brains. Our results support that endogenous and applied EFs are important considerations for designing cell therapies for tissue repair in vivo.